There is something I don't understand. Isn't there a contradiction between the cause of our fatigue being "sickness syndrome" and the research that has shown mitochondrial dysfunction (e.g. Sarah Myhill)? I mean one says we feel fatiguebecause chemical messengers are being fired which increase the perception of fatigue, whereas the other is saying we feel fatigue because we actually cannot produce energy at a sub-cellular level.

There is something I don't understand. Isn't there a contradiction between the cause of our fatigue being "sickness syndrome" and the research that has shown mitochondrial dysfunction (e.g. Sarah Myhill)? I mean one says we feel fatiguebecause chemical messengers are being fired which increase the perception of fatigue, whereas the other is saying we feel fatigue because we actually cannot produce energy at a sub-cellular level.

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I don't think anyone is claiming that sickness response is responsible for all ME symptoms, but might be involved in some symptoms.

There is something I don't understand. Isn't there a contradiction between the cause of our fatigue being "sickness syndrome" and the research that has shown mitochondrial dysfunction (e.g. Sarah Myhill)? I mean one says we feel fatiguebecause chemical messengers are being fired which increase the perception of fatigue, whereas the other is saying we feel fatigue because we actually cannot produce energy at a sub-cellular level.

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What makes you think that the cytokines responsible for sickness behaviour don't induce it by acting on mitochondria? Maybe the perception of fatigue isn't just a brain thing but is actually fatigue. In any case, one doesn't necessarily exclude the other. As usual, the situation is unclear and we need more research.

What makes you think that the cytokines responsible for sickness behaviour don't induce it by acting on mitochondria? Maybe the perception of fatigue isn't just a brain thing but is actually fatigue. In any case, one doesn't necessarily exclude the other. As usual, the situation is unclear and we need more research.

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I considered that might be the case, but the way sickness behaviour is usually explained is as a mechanism to "tell the body it needs to rest to conserve energy to fight the infection" etc. Actually damaging/impairing mitochondria seems like it would not be the best way of telling us we need to rest

Two thoughts spring to mind here:
1. This explains why we FEEL sick...
2. How could this explain genuine exhaustion in which one CANNOT override the feeling is is forced to stop (e.g. total loss of muscular strength).

There is something I don't understand. Isn't there a contradiction between the cause of our fatigue being "sickness syndrome" and the research that has shown mitochondrial dysfunction (e.g. Sarah Myhill)? I mean one says we feel fatiguebecause chemical messengers are being fired which increase the perception of fatigue, whereas the other is saying we feel fatigue because we actually cannot produce energy at a sub-cellular level.

Click to expand...

What makes you think that the cytokines responsible for sickness behaviour don't induce it by acting on mitochondria? Maybe the perception of fatigue isn't just a brain thing but is actually fatigue. In any case, one doesn't necessarily exclude the other. As usual, the situation is unclear and we need more research.

Click to expand...

High levels of mito activity are needed for immune response (both humeral and febrile). Hence sickness response forcing rest makes biological/evolutionary sense) but sickness repsonse lowering energy production does not - it would destroy immune response as occurs in ME patients.

There is something I don't understand. Isn't there a contradiction between the cause of our fatigue being "sickness syndrome" and the research that has shown mitochondrial dysfunction (e.g. Sarah Myhill)? I mean one says we feel fatiguebecause chemical messengers are being fired which increase the perception of fatigue, whereas the other is saying we feel fatigue because we actually cannot produce energy at a sub-cellular level.

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I am inclined to agree Cigana, poor mito function inducing sickness response would make sense to protect vital functions. Poor mito function reducing immune response and cause extended symptoms via sickness response would also make sense. Sickness response causing poor mito function would be an evolutionary disaster other than by safe mechanisms such as thyroid hormones and melatonin.

Two thoughts spring to mind here:
1. This explains why we FEEL sick...
2. How could this explain genuine exhaustion in which one CANNOT override the feeling is is forced to stop (e.g. total loss of muscular strength).

Any thoughts Simon?

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Couple of thoughts from me
1. Microglia/sickness response is unlikely to be a complete explanation. As Jarred Younger stressed in his presentation in California, there is considerable overlap between sickness response and mecfs/FM, but it isn't complete by any means.
2. Also, sickness response doesn't have a single level: it can be mild and it can also be severe and incapacitating. I'm not quite sure of the difference between exhaustion and 'genuine' exhaustion, but it's possible that severe sickness response could explain genuine exhaustion too. So far, though, this central role of sickness response in mecfs is very much a plausible but untested hypothesis.

Couple of thoughts from me
1. Microglia/sickness response is unlikely to be a complete explanation. As Jarred Younger stressed in his presentation in California, there is considerable overlap between sickness response and mecfs/FM, but it isn't complete by any means.
2. Also, sickness response doesn't have a single level: it can be mild and it can also be severe and incapacitating. I'm not quite sure of the difference between exhaustion and 'genuine' exhaustion, but it's possible that severe sickness response could explain genuine exhaustion too. So far, though, this central role of sickness response in mecfs is very much a plausible but untested hypothesis.

Click to expand...

I think we are pretty much on the same page given your response above Simon.

I refer to "genuine" exhaustion in the true meaning of the term - absolutely no energy left if the house were burning down, one would have to be carried out. I did used to experience that degree of exhaustion as opposed to the severe fatigue accompanying heavy infection that may be mis-labelled as exhaustion.

Hyperbole in general use of language sometimes makes finding the right phrasing with severe ME difficult doesn't it?